In vivo and in vitro studies in our laboratory have demonstrated the presence of specific collagenolytic activity in invasive human and animal tumors as opposed to noninvasive benign tumors of similar origin. Neutral proteases were also found. We propose to continue the biochemical characterization of components of the collagenolytic system associated with select invasive human and animal tumors; to compare the properties of these components with those of the corresponding normal and benign tumor tissues; to correlate the level of the collagenolytic activity with tumor growth and invasion; to determine the distribution of these enzymes and their precursor molecules in the tumor parenchyma and the surrounding stroma; and to study the possible mechanism(s) regulating its activity. It is proposed that benign tumors which have malignancy potential, may contain precursors or inactive forms of these collagenolytic enzymes which may become activated during transformation by some mechanism to be investigated. The possibility that collagenolytic enzymes of host origin function in invasive tumor growth also will be explored. Rabbit shope virus papilloma (a benign tumor) and its invasive counterpart, the fast growing VX-2 carcinoma will continue to be used as an experimental model system for the study of these mechanisms and to test our hypothesis. It is hoped that with full characterization of various components of the collagenolytic system and the understanding of the mechanism of control of synthesis and release of these components, tumor growth and invasion could be limited and more successful removal of the primary lesion may then be possible.